J Korean Diabetes Assoc.  2007 Jul;31(4):351-361. 10.4093/jkda.2007.31.4.351.

In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications

• Nam JS
• Cho YJ
• Noh TW
• Kim CS
• Park JS
• Cho MH
• Kim HJ
• Yoon JE
• Jung HY
• Kang ES
• Rhee YM
• Lee HK
• Ahn CW
• Cha BS
• Lee EJ
• Lim SK
• Kim KR
• Lee HC

• KMID: 2222523
• DOI: http://doi.org/10.4093/jkda.2007.31.4.351

Abstract

BACKGROUND: In vivo corneal confocal microscopy (IVCCM) is being recognized as a non-invasive, early diagnostic tool for diabetic neuropathy, for it provides a clear image of corneal subbasal nerve plexus in detail. Nerve growth factors (NGF) are believed to regulate peripheral and central nervous system, neuronal differentiation, and regeneration of damaged nerves, and their role in diabetic neuropathy is being emphasized these days. Moreover, NGFs and receptors are also expressed in retina and renal mesangial cells, suggesting their possible role in the common pathogenesis of diabetic microvascular complications. We plan to examine corneal structures of diabetic patients and compare IVCCM with conventional tools and analyze their serum and tear NGF levels.
METHODS
IVCCM, nerve conduction velocity (NCV), and serum, urine, and tear samplings were done to 42 diabetic patients. From IVCCM, we measured corneal nerve density, branch, and tortuosity, total corneal/epithelial thickness, and the number of endothelial/keratocyte cells, and we checked patients' biochemical profiles and serum and tear NGF levels.
RESULTS
Patients with more severe neuropathy had less corneal endothelial cells (3105 +/- 218 vs. 2537 +/- 142 vs. 2350 +/- 73/mm3 vs. 1914 +/- 465/mm3, P = 0.02), higher serum NGF (36 +/- 15 vs. 60 +/- 57.66 vs. 80 +/- 57.63 vs. 109 +/- 60.81 pg/mL, P = 0.39) and tear NGF levels (135.00 +/- 11.94 vs. 304.29 +/- 242.44 vs. 538.50 +/- 251.92 vs. 719.50 +/- 92.63 pg/mL, P = 0.01). There was a positive correlation between neuropathy and corneal nerve tortuosity (r2 = 0.479, P = 0.044) and negative correlation between neuropathy and endothelial cell count (r2 = -0.709, P = 0.002). Interestingly, similar changes were seen in other microvascular complications as well.
CONCLUSION
Our results provide a possibility of using novel tools, IVCCM and NGF, as common diagnostic tools for diabetic microvascular complications, but it should be followed by a large population study.

Keyword

Diabetic microvascular complications; In vivo corneal confocal microscopy; Nerve growth factor

MeSH Terms

Central Nervous System
Diabetic Neuropathies
Endothelial Cells
Humans
Mesangial Cells
Microscopy, Confocal*
Nerve Growth Factor*
Nerve Growth Factors
Neural Conduction
Neurons
Regeneration
Retina
Tears
Nerve Growth Factor
Nerve Growth Factors

Figure

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  Fig. 1 Corneal subbasal nerve plexus of a patient with mild diabetic neuropathy by in vivo corneal confocal microscopy. Two nerve fibers are seen with no nerve fiber branching and mild tortuosity.

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  Fig. 2 Relationships between endothelial cell count (A) and tortuosity (B) and severity of neuropathy. There is a negative correlation between endothelial cell count and severity of neuropathy and a positive correlation between tortuosity and severity of neuropathy. NCV: O, normal; 1, mild neuropathy; 2, moderate neuropathy; 3, severe neuropathy.

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  Fig. 3 Relationship between tear NGF level and neuropathy. There is a positive correlation between tear NGF level and neuropathy.

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  Fig. 4 Relationships between serum and tear NGF and other microvascular complications. (A, serum NGF vs. DMR; B, serum NGF vs. DMN; C, tear NGF vs. DMN; D, tear NGF vs. 24-hour albuminuria, DMR: O, normal, 1, non-proliferative retinopathy; 2, proliferative retinopathy)

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